Plasma Amyloid-β (Aβ₄₂) Correlates with Cerebrospinal Fluid Aβ₄₂ in Alzheimer’s Disease

Article type: Research Article

Authors: Teunissen, Charlotte E.^{a; *} | Chiu, Ming-Jang^{b; c; d} | Yang, Che-Chuan^e | Yang, Shieh-Yueh^e | Scheltens, Philip^f | Zetterberg, Henrik^{g; h; i; j} | Blennow, Kaj^{g; h}

Affiliations: [a] Department of Clinical Chemistry, Neurochemistry Laboratory and Biobank, Amsterdam Neuroscience, VU University Medical Center Amsterdam, The Netherlands | [b] Department of Neurology, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan | [c] Graduate Institute of Brain of Mind Sciences, College of Medicine, National Taiwan University, Taipei, Taiwan | [d] Department of Psychology, National Taiwan University, Taipei, Taiwan | [e] MagQu Co., Ltd., New Taipei City, Taiwan | [f] Department of Neurology, Alzheimer’s Center, VU University Medical Center, Amsterdam Neuroscience, Amsterdam, The Netherlands | [g] Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden | [h] Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, University of Gothenburg, Mölndal, Sweden | [i] Department of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London, UK | [j] UK Dementia Research Institute, London, UK

Correspondence: [*] Correspondence to: Charlotte E. Teunissen, Neuroscience, VU University Medical Center Amsterdam, The Netherlands. E-mail: c.teunissen@vumc.nl.

Abstract: The 42 amino acid form of amyloid-β (Aβ42) plays a key role in the pathogenesis of Alzheimer’s disease (AD) and is a core biomarker for the diagnosis of AD. Numerous studies have shown that cerebrospinal fluid (CSF) Aβ42 concentrations are decreased in AD, when measured by enzyme-linked immunosorbent assay (ELISA) and other conventional immunoassays. While most studies report no change in plasma Aβ42, independent studies using the immunomagnetic reduction (IMR) technique report an increase in plasma Aβ42 levels in AD. To confirm the opposite changes of Aβ42 levels in CSF and plasma for AD, we assayed the levels of Aβ42 in plasma of subjects with known CSF Aβ42 levels. In total 43 controls and 63 AD patients were selected at two sites: the VU University Medical Center (n = 55) and Sahlgrenska University Hospital (n = 51). IMR and ELISA were applied to assay Aβ42 in plasma and CSF, respectively. We found a moderately negative correlation between plasma and CSF Aβ42 levels in AD patients (r = –0.352), and a weakly positive correlation in controls (r = 0.186). These findings further corroborate that there are opposite changes of Aβ42 levels in CSF and plasma in AD. The possible causes for the negative correlation are discussed by taken assay technologies, Aβ42 transport from brain to peripheral blood, and sample matrix into account.

Keywords: Amyloid-β , cerebrospinal fluid, immunomagnetic reduction, plasma

DOI: 10.3233/JAD-170784

Journal: Journal of Alzheimer's Disease, vol. 62, no. 4, pp. 1857-1863, 2018